The Systems Biology of COVID-19 and the SARS-CoV-2 virus. The class will build a foundation that includes the emergence of complexity, simple biological subsystems, their reductionist and equivalent toy and organ-chip models, and the measurements required to specify model architecture and parameters. Applications to biology, physiology, medicine, chemical and biological defense, pharmacology, drug discovery, and toxicology. UGrad: PHYS 240 01 and BME 290B; Grad: PHYS 326 and BME 395C.
Kate Jones
ReplyDeleteAssignment 19A Article 15
Knew: Noise can affect cell fate and is important to incorporate into models of genetic networks. The axis of Fig3A makes sense to me because if the intensities of the indicators are not equal, there would be different amounts of noise present within the cell or the environment.
Learned: All cells possess both intrinsic and extrinsic noise because the intrinsic noise of one cell becomes the extrinsic noise of cells around it. I liked the definition of intrinsic noise because it helped me narrow down exactly which variables contribute to intrinsic versus extrinsic noise (p 1184).
Pressing Questions: Of course removing or inhibiting a repressor will increase the amount of product produced--are we just looking at the relationship between the color of the bacteria indicative of the source of noise and comparing it to the output of protein?
Presentation: I like all of the plots in figure three because they very clearly show how the researchers determined extrinsic and intrinsic noise as well as the relationships between fluorescence and intrinsic and extrinsic noise when a repressor is and is not present.
Thoughts: This was an interesting way to show the effects of intrinsic and extrinsic noise because any shift in expression as a result of intrinsic noise would produce one colored protein and extrinsic noise would cause another colored protein. This paper shows the influence noise in the environment as well as differences from cell to cell can have on gene expression, and this should be taken into account when modeling.
Tim Lee
ReplyDeleteAsgn_19A
0. Knew: Noise in gene expression is an inherent trait of all cells and can influence cell fate.
1. Learned: Noise can be characterized by internal or external noise. Transcription rate, regulatory dynamics, and genetic factors control the amplitude of noise. Noisiness in a cell is genetically determined. Noise produces a trade off for predictability for heterogeneity.
2. Pressing: I'm confused to how they understood which fluorescence expression correlated to just internal noise or external noise. They gave good definitions for what each noise type represents but I'm having trouble seeing how they measured each type separately.
3. Presentation: Definition of external and internal gene expression noise and quantification through fluorescent proteins in E. coli
4. Thoughts: It was very helpful for me to understand the different kinds of noise and how they can come about.
James Pino
ReplyDeleteAsgn_19A
0: Knew: Noise contributes to cell variablitly. This noise is both intrinsic and extrinsic.
1:Learned: How to distinguish between intrinsic and extrinsic. How feedback increases intrinsic noise. Intrinsic and extrinsic noise don't have to correlate.
2:Pressing: Where do the parameters C1 and C2 come from?
3: Presentation: How to model intrinsic and extrinsic noise.
4:Thoughts: This proved great in this system. Have there been attempts to see how noise in multiple species within the cell act?
Juan Gnecco
ReplyDeleteAsgn_19A
0: knew: that stochastic effects determine the noise and the expression profile of cells temporarily at any specific time point
1: Learned: the amount of noise is being studied to determine cell profiles.
2: Pressing: In pathology, should we focus on the noise to define disease states? How do we determine how much noise is just noise particularly if genes are interacting? Do gene expression patterns modulate or "synchronize" the cells in a system?
3: presenation: extrinsic/intrisic noise in vivo polarized organs
4.Throughts: What about alternative pathways and expresssion of genes by multiple TFs?
Juan Gnecco
ReplyDeleteAsgn_19A
0: knew: that stochastic effects determine the noise and the expression profile of cells temporarily at any specific time point
1: Learned: the amount of noise is being studied to determine cell profiles.
2: Pressing: In pathology, should we focus on the noise to define disease states? How do we determine how much noise is just noise particularly if genes are interacting? Do gene expression patterns modulate or "synchronize" the cells in a system?
3: presenation: extrinsic/intrisic noise in vivo polarized organs
4.Throughts: What about alternative pathways and expresssion of genes by multiple TFs?
Cameron Togrye
ReplyDeleteAsgn_19A / Stochastic Gene Expression
0. Knew: Basics of the Lac Operon and its repressor
1. Learned: It is interesting to see that intrinsic noise is so well correlated with transcription levels. However, I was still unclear on why extrinsic experienced a peak when it came to noise and transcription levels.
2. In Figure 1A, I am not sure what exactly represents intrinsic noise. Why isn't the noise just the fluctuation of the GFP itself? Also, why were two GFP's needed when one could just observe fluctuations in a single reporter GFP? Also, I was also a little unclear on what metric they were using to represent extrinsic cell-cell differences.
3. Presentation: Description of the Lac Operon
4. Thoughts: Are there ways to diminish noise (say for example if you were trying to minimize differentiation rate) while also not diminishing transcription rate? What if you need a certain level of transcription for continued viability but also need reduced noise?
Arman Chowdhury
ReplyDeleteAssignment 19 A
0. Knew: Stochasticity arises from biochemical process of gene expression (intrinsic noise) and fluctuations in other cellular components (extrinsic noise), and both contribute to overall variation.
1. Learned: Noise can be quantitatively defined as standard deviation divided by mean, calculated from the distribution of proteins produced from gene expression. As rate of transcription increases total noise (intrinsic + extrinsic) decreases (as plot 3B shows). Regulatory dynamics and genetic factors also contribute towards amplitude of noise.
2. Pressing ?: They measured intrinsic noise independent of extrinsic noise (by providing identical intracellular environment, including same promoters, thus removing extrinsic noise), and extrinsic noise independent of intrinsic noise (by choosing identical regulatory networks). So on Waddington’s model, if extrinsic noise causes a change in heights of hills and valleys, how would intrinsic noise bring change to the landscape?
3. Presentation: Plots and images helped me visualize the relationship between fluorescence and noise, and are well explained.
4. Thoughts: Fig 2A of the article shows different cells showing different levels of noise. I wonder how this affects the collective function and properties of a population of cells.
Selene van der Walt
ReplyDeleteAssignment 19 A
0. Knew: noise in gene expression exists and can be responsible for altering expression levels enough to move cells to a different 'attractor basin' as discussed in previous papers.
1. Learned: Extrinsic noise is global to a single cell due to feedback interactions between caused by differing expression levels, but varies across cells. Intrinsic noise is a failure to correlate of two of the same gene in the same environment. Intrinsic noise decreases as the amount of transcript increases, and both these types of noise can be tracked individually within a cell.
2. Pressing ?: How exactly were they able to distinguish between intrinsic and extrinsic noise in their experiment? Which type of noise was the noise we were discussing when talking about Waddington's landscape? Or was it both combined together?
3. Presentation: Modeling transcriptional regulatory circuits, and the relationships between regulatory dynamics and noise.
4. Thoughts: This was an very interesting, concise paper, I enjoyed reading it. Noise is not something I had previously thought could explain genetic variation.
Priyanka Ravichandran
ReplyDeleteAsgn 19A
0. Knew - about the Lac operon and that noise affects cell variability
1. Learned - how the concepts of intrinsic and extrinsic noise apply to gene expression; amount of noise in a cell is genetically determined; regulatory dynamics can significantly affect noise levels in cells
2. Questions - What value of Nint means there is a significant level of noise?
3. Presentation - modeling intrinsic and extrinsic noise in E.coli strains
4. Comments - This article was helpful in learning about the different types of noise.
Zach Bednarke
ReplyDeleteasgn A19
0- I knew that noise affects gene expression levels,
1- Learned to consider that the intrinsic noise of one gene serves as extrinsic noise to others in a genome. Gained the intuition of how the number of transcripts relates inversely to amount of intrinsic noise.
2- What exactly is the Lac operon? Would amount of noise at any point in gene space S correspond to greater gradient on landscape? Or would it bring altitudes closer together?
3- Lac operon
4- reading this paper, i realized about halfway through that I had a solid understanding of the basic biology of the system, which symbolizes a big victory for me. But in this paper, it seemed like the results were very intuitive. I had no trouble grasping the concept once I had a handle on the biological setting in which the experiment took place.